Oleuropein modulates apoptotic and endothelial-associated markers in a radiation-induced acute renal injury model in rats.

PURPOSE: Radiation-induced renal injury (RIN) is a major clinical concern, particularly in cancer patients undergoing radiotherapy, where radiation triggers oxidative stress, inflammatory cascades, apoptosis and endothelial dysfunction, leading to progressive renal damage. Oleuropein (OLE), a polyphenolic compound derived from olive leaves, has demonstrated potent antioxidant, anti-inflammatory and anti-apoptotic properties in various preclinical models. However, its radioprotective potential against renal toxicity remains poorly understood. This study aimed to investigate the protective effects of OLE in a radiation-induced acute renal injury model by evaluating apoptotic regulation, endothelial-associated marker expression and renal function. MATERIALS AND METHODS: Forty-eight male Wistar Albino rats were randomly assigned to four groups: Control, OLE (50 mg/kg/day for 4 weeks), Radiation (6 Gy single dose total-body gamma irradiation) and OLE+Radiation (OLE treatment 1 week before and 3 weeks after irradiation). Renal function was assessed via serum urea, BUN and creatinine levels. Histopathological, PAS and immunohistochemical (Cyclin D1, CD31) analyses were performed. Gene expression of apoptotic markers BAX and BCL2 was quantified by RT-qPCR. Data were analyzed using ANOVA and nonparametric tests where appropriate (p < .05). RESULTS: Radiation significantly increased serum BUN, creatinine and urea levels (p < .001), disrupted renal histoarchitecture and elevated Cyclin D1 and CD31 expression. RT-qPCR showed an increased pro-apoptotic BAX/BCL2 ratio in the RAD group. OLE treatment attenuated radiation-associated biochemical alterations and reduced the severity of histopathological changes based on semi-quantitative scoring, accompanied by decreased Cyclin D1 and CD31 expression. Importantly, OLE restored the apoptotic balance by downregulating BAX and upregulating BCL2, thereby significantly reducing the BAX/BCL2 ratio. CONCLUSION: These findings indicate that OLE exerts radioprotective effects in a radiation-induced acute renal injury model by modulating apoptotic signaling, influencing endothelial-associated marker expression and improving renal biochemical parameters. Further mechanistic and long-term studies are warranted to clarify its potential therapeutic relevance in radiation-associated renal injury.